ヒトの細胞サイクル制御フォスファタゼの触媒ドメインの結晶構造,Cdc25A
E B Fauman1, J P Cogswell, B Lovejoy
1Department of Biological Chemistry, The University of Michigan, Ann Arbor 48109-1055, USA. fauman@umich.edu
Cell
|May 30, 1998
まとめ
人間のCdc25Aフォスファタゼ構造は,他のフォスファタゼとは異なるが,硫黄転送タンパク質に類似する新しい折り目を明らかにする. この発見は,細胞サイクル調節と潜在的な自己抑制メカニズムについての洞察を提供します.
科学分野:
- バイオケミストリー バイオケミストリー
- 構造生物学 構造生物学とは
- 細胞生物学 細胞生物学
背景:
- Cdc25フォスファタゼは,細胞分裂キナーゼの重要な調節体である.
- その構造を理解することは,細胞サイクル制御の解読の鍵です.
研究 の 目的:
- 人間のCdc25A触媒領域の3D構造を決定する.
- Cdc25Aの酵素活性と調節の構造的基礎を解明する.
主な方法:
- 2.3Aの解像度のX線結晶学.
- 構造に基づくシーケンスアライナメント.
主要な成果:
- 人間のCdc25A触媒ドメインは,ロダネス菌に似たユニークなアルファ/ベータの折りたたみを持ち,以前はリン酸塩酸で観察されていなかった.
- Cys-430とCys-384の間の二硫化結合は,酸化ストレスによる自己抑制メカニズムの可能性を示唆しています.
- Asp-383は構造的な役割を果たし,一般的な酸として作用しません; Glu-431は一般的な酸として提案されています.
結論:
- Cdc25A構造は,フォスファタゼ分類に意味を持つ新しい折り目を明らかにします.
- この発見は,酸化ストレスを含む規制メカニズムを示唆し,MAPキナーゼファスファタゼとACR2.2との潜在的な構造的同質性を特定しています.
関連する概念動画
01:45Positive Regulator Molecules
100.8K
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
100.8K
02:54Protein Kinases and Phosphatases
12.1K
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
12.1K
02:39Positive Regulator Molecules
5.3K
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
5.3K
02:34Inhibition of Cdk Activity
4.8K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
02:17Separation of Sister Chromatids
3.6K
At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
At the onset of anaphase, separase, a proteolytic enzyme, is...
3.6K
00:50Anaphase Promoting Complex
2.5K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
2.5K